Details
| Original language | English |
|---|---|
| Pages (from-to) | 20-28 |
| Number of pages | 9 |
| Journal | Cancer letters |
| Volume | 399 |
| Early online date | 10 Apr 2017 |
| Publication status | Published - 28 Jul 2017 |
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G1/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.
Keywords
- Argyrin F, Chemotherapy, PDAC, Therapeutic efficacy
ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Biochemistry, Genetics and Molecular Biology(all)
- Cancer Research
Sustainable Development Goals
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In: Cancer letters, Vol. 399, 28.07.2017, p. 20-28.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Therapeutic effects of Argyrin F in pancreatic adenocarcinoma
AU - Chen, Xi
AU - Bui, Khac Cuong
AU - Barat, Samarpita
AU - Thi Nguyen, Mai Ly
AU - Bozko, Przemyslaw
AU - Sipos, Bence
AU - Kalesse, Markus
AU - Malek, Nisar P.
AU - Plentz, Ruben R.
N1 - Publisher Copyright: © 2017 Elsevier B.V. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/7/28
Y1 - 2017/7/28
N2 - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G1/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.
AB - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G1/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.
KW - Argyrin F
KW - Chemotherapy
KW - PDAC
KW - Therapeutic efficacy
UR - http://www.scopus.com/inward/record.url?scp=85018562491&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2017.04.003
DO - 10.1016/j.canlet.2017.04.003
M3 - Article
C2 - 28408354
AN - SCOPUS:85018562491
VL - 399
SP - 20
EP - 28
JO - Cancer letters
JF - Cancer letters
SN - 0304-3835
ER -